Burimamide (IIa) was the first clinically effective H.sub.2 -receptor antagonist. It inhibits gastric secretion in animals and man, but oral absorption is poor. ##STR2## Metiamide (IIb), a subsequently evaluated H.sub.2 -antagonist, is more potent than burimamide and is orally active in man. Clinical utility was limited, however, owing to toxicity (agranulocytosis). Cimetidine (IIc) is as effective an H.sub.2 -antagonist as metiamide, without producing agranulocytosis, and has recently been marketed as an anti-ulcer drug.
Reviews on the development of H.sub.2 -antagonists, including those discussed in the preceding paragraph, may be found in C. R. Ganellin, et al., Federation Proceedings, 35, 1924 (1976), in Drugs of the Future, 1, 13 (1976), and in references cited therein. Relevant patents are as follows:
(A) U.S. Pat. No. 4,062,863 discloses histamine H.sub.2 -antagonists of the formula ##STR3## wherein R is hydrogen, (lower)alkyl or (CH.sub.2).sub.2 Z'CH.sub.2 -HET'; Z and Z' each are sulfur or methylene; and HET and HET' each are an imidazole ring optionally substituted by methyl or bromo, a pyridine ring optionally substituted by hydroxy, methoxy, chloro or bromo, a thiazole ring or an isothiazole ring, and pharmaceutically acceptable acid addition salts thereof. U.S. Pat. Nos. 4,120,968, 4,120,973 and 4,166,857 are divisionals thereof which have substantially the same disclosure.
(B) U.S. Pat. No. 4,242,350 discloses histamine H.sub.2 -antagonists of the formula ##STR4## in which Y is an oxygen or sulphur atom, a direct bond or a methylene or sulphinyl radical; m is 0 to 4 and n is 1 to 4, provided that when Y is a sulphur or oxygen atom or a sulphinyl radical m is 1 to 4, and when Y is an oxygen atom or a sulphinyl radical n is 2 to 4;
R.sup.1 is a hydrogen atoms or an alkyl radical of 1 to 10 carbon atoms; PA1 A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C=Z in which Z is an oxygen or a sulphur atom or a radical of the formula NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.2, NCO.sub.2 R.sup.2, NSO.sub.2 R.sup.2 or NR.sup.3 in which R.sup.2 is an alkyl radical of 1 to 6 carbon atoms or an aryl radical of 6 to 12 carbon atoms and R.sup.3 is a hydrogen atom or an alkyl radical of 1 to 6 carbon atoms; PA1 B is an alkoxy or alkylthio radical of 1 to 6 carbon atoms or a radical of the formula NR.sup.4 R.sup.5 in which R.sup.4 and R.sup.5, which may be the same or different, are hydrogen atoms, alkyl radicals of 1 to 10 carbon atoms, alkenyl or alkynyl radicals of 3 to 6 carbon atoms in which the double or triple bond respectively is separated from the nitrogen atom of NR.sup.4 R.sup.5 by at least one carbon atom, (primary hydroxy)alkyl or (primary amino)alkyl radicals of 2 to 6 carbon atoms or cycloalkyl radicals of 3 to 6 carbon atoms, or R.sup.4 and R.sup.5 are joined to form, together with the nitrogen atom to which they are attached, a 5- or 6-membered saturated ring which optionally contains an additional oxygen atom or NH radical; and the pharmaceutically-acceptable acid-addition salts thereof. PA1 m is 0 to 4 and n is 1 to 4, provided that when Y is a sulphur, oxygen or a sulphinyl radical, m is 1 to 4 and when Y is oxygen or a sulphinyl radical n is 2 to 4; PA1 R.sup.1 is a hydrogen, halogen, or alkyl of 1 to 6 carbon atoms; PA1 R.sup.2 is hydrogen, alkyl of 1 to 10 carbon atoms, alkanoyl of 1 to 6 carbon atoms or aroyl of 7 to 11 carbon atoms; PA1 A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C=Z in which Z is an oxygen or sulphur atom or a radical of the formula NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.3, -NCO.sub.2 R.sup.3, NSO.sub.2 R.sup.3 or NR.sup.4 in which R.sup.3 is alkyl of 1 to 6 carbon atoms or aryl of 6 to 12 carbon atoms and R.sup.4 is hydrogen or alkyl of 1 to 6 carbon atoms; PA1 B is alkoxy or alkylthio of 1 to 6 carbon atoms or a radical of the formula NR.sup.5 R.sup.6 in which R.sup.5 and R.sup.6, which may be the same or different, are hydrogen, alkyl of 1 to 10 carbon atoms, alkenyl of 3 to 10 carbon atoms in which the double bond is separated from the nitrogen atom of NR.sup.5 R.sup.6 by at least one carbon atom, cycloalkyl of 3 to 8 carbon atoms, (primary hydroxy)alkyl of 2 to 6 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NR.sup.5 R.sup.6 by at least two carbon atoms, alkoxyalkyl of 3 to 10 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NR.sup.5 R.sup.6 by at least two carbon atoms; or dialkylaminoalkyl of 4 to 10 carbon atoms in which the nitrogen atom is separated from the nitrogen atom of NR.sup.5 R.sup.6 by at least two carbon atoms; and the pharmaceutically-acceptable acid-addition salts thereof. PA1 A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C=Z in which Z is an oxygen or sulphur atom or a radical of the formula NCN, NNO.sub.2 CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, or NCOR.sup.1, NCO.sub.2 R.sup.1, NSO.sub.2 R.sup.1 or NR.sup.2 in which R.sup.1 is an alkyl radical of 1 to 6 carbon atoms or an aryl radical of 6 to 12 carbon atoms and R.sup.2 is a hydrogen atom or an alkyl radical of 1 to 6 carbon atoms; PA1 B is an alkoxy or alkylthio radical of 1 to 6 carbon atoms or a radical of the formula NHR.sup.3 in which R.sup.3 is a hydrogen atom or an alkyl radical of 1 to 10 carbon atoms; and the pharmaceutically-acceptable acid addition salts thereof. PA1 Y is nitrogen or a CH radical; PA1 n is 1, 2, 3 or 4; PA1 m is 0 or 1; PA1 R.sup.1 is hydrogen, alkyl of 1 to 6 carbon atoms or alkoxyalkyl of 3 to 10 carbon atoms in which the oxygen atom is separated from the nitrogen atom of the guanidine residue by at least two carbon atoms; PA1 R.sup.2 is a radical of the formula -A-B in which A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C=Z in which Z is oxygen, sulphur or a radical of the formula NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.3, NCO.sub.2 R.sup.3, NSO.sub.2 R.sup.3 or NR.sup.4 in which R.sup.3 is alkyl of 1 to 6 carbon atoms, phenyl or a monocyclic heteroaromatic ring containing one or two hetero atoms selected from oxygen, nitrogen and sulphur and R.sup.4 is hydrogen or alkyl of 1 to 6 carbon atoms; PA1 B is alkyl, alkoxy or alkylthio of 1 to 6 carbon atoms or a radical of the formula NHR.sup.5 in which R.sup.5 is hydrogen or alkyl of 1 to 6 carbon atoms, alkenyl or alkynyl of 3 to 10 carbon atoms in which the double or triple bond is separated from the nitrogen atom of NHR.sup.5 by at least one carbon atom, cycloalkyl of 3 to 6 carbon atoms, (primary hydroxy)alkyl or (primary amino)alkyl of 2 to 6 carbon atoms, heteroalkyl of 1 to 6 carbon atoms, alkoxyalkyl of 3 to 6 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NHR.sup.5 by at least two carbon atoms, phenylalkyl or monocyclic aromatic heterocyclalkyl in which the alkyl part is of 1 to 6 carbon atoms, the phenyl ring carries an optional halogen and the heterocyclic ring contains one or two hetero atoms selected from oxygen, nitrogen and sulphur, or R.sup.5 is a benzoylaminoalkyl or benzenesulphonylaminoalkyl in which the alkyl part is of 2 to 6 carbon atoms and the benzene ring carries an optional chlorine substituent, or a radical of the formula: ##STR8## in which X, Y, n, m and R.sup.1 have the meanings give above, p is 2 to 12 and G is sulphur or methylene; or R.sup.2 is a radical of the formula: ##STR9## and the pharmaceutically acceptable acid addition salts thereof. PA1 Y is nitrogen or a radical of the formula CH or CCH.sub.3 ; m is 0 or 1; PA1 R.sup.1 is hydrogen and R.sup.2 is cyano, trifluoroacetyl, alkanoyl of 1 to 6 carbon atoms or 4,5-dihydro-4-oxothiazol-2-yl, or --R.sup.2 is a radical of the formula -A-B in which A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C=Z in which PA1 Z is oxygen, sulphur or a radical of the formula NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.6, NCO.sub.2 R.sup.6, NSO.sub.2 R.sup.6 or NR.sup.7 in which R.sup.6 is alkyl of 1 to 6 carbon atoms and R.sup.7 is a hydrogen or alkyl of 1 to 6 carbon atoms and B is alkyl, alkoxy or alkylthio of 1 to 6 carbon atoms or a radical of the formula NR.sup.8 R.sup.9 in which R.sup.8 and R.sup.9, which may be the same or different, are hydrogen, alkyl of 1 to 10 carbon atoms, alkenyl or alkynyl of 3 to 10 carbon atoms in which the double or triple bond is separated from the nitrogen atom of NR.sup.8 R.sup.9 by at least one carbon atom, (primary hydroxy)alkyl of 2 to 6 carbon atoms, alkoxyalkyl of 3 to 10 carbon atoms in which the oxygen atom is separated from the nitrogen atom of NR.sup.8 R.sup.9 by at least two carbon atoms, or pyridylmethyl radicals, or, when R.sup.9 is hydrogen, R.sup.8 is 2-[(5-dimethylaminomethylfuran-2-yl)methylthio]-ethylamino, or R.sup.8 and R.sup.9 may be joined together to form a 5- or 6-membered non-aromatic ring which optionally contains an additional nitrogen or oxygen atom; or R.sup.1 and R.sup.2, taken together represent an imidazolidin-2-ylidene radical: PA1 R.sup.3 is hydrogen or fluorine; PA1 R.sup.4 is hydrogen or, when R.sup.3 is hydrogen, R.sup.4 is halogen or methyl; PA1 R.sup.5 is hydrogen, alkyl of 1 to 6 carbon atoms or alkoxyalkyl of 3 to 10 carbon atoms in which the oxygen atom is separated from the nitrogen atom of the guanidine residue by at least two carbon atoms; PA1 Y.sup.1 and Y.sup.2, which may be the same or different, are oxygen, sulphur, direct bonds or methylene or sulphinyl radicals; m and p, which may be the same or different, are 0 to 4, and n and q, which may be the same or different, are 1 to 4, provided that when Y.sup.1 or Y.sup.2 is oxygen, sulphur or a sulphinyl radical, m or p respectively is 1 to 4 and provided that when Y.sup.1 or Y.sup.2 is oxygen or a sulphinyl radical, n or q respectively is 2 to 4; PA1 one of R.sup.1 and R.sup.2 is hydrogen and the other is a hydrogen or alkyl of 1 to 6 carbon atoms; PA1 A is a 3,4-dioxocyclobuten-1,2-diyl radical or a radical of the formula C=Z in which Z is sulphur, oxygen or a radical of the formula NCN, NNO.sub.2, CHNO.sub.2, NCONH.sub.2, C(CN).sub.2, NCOR.sup.3, NCO.sub.2 R.sup.3, NSO.sub.2 R.sup.3 or NR.sup.4 in which R.sup.3 is alkyl of 1 to 6 carbon atoms or aryl of 6 to 12 carbon atoms and R.sup.4 is hydrogen or alkyl of 1 to 6 carbon atoms, or when R.sup.1 and R.sup.2 are both hydrogen --A-- represents a radical of the formula: EQU --A.sup.1 --E.sup.1 --G--E.sup.2 --A.sup.2 -- PA1 in which PA1 A.sup.1 and A.sup.2, which may be the same or different, are 3,4-dioxocyclobuten-1,2-diyl radicals or radicals of the formula C=Z.sup.1 and C=Z.sup.2 respectively in which Z.sup.1 and Z.sup.2, which may be the same or different, have one of the values given above for Z, E.sup.1 and E.sup.2, which may be the same or different, are oxygen, sulphur or NH radicals optionally substituted by alkyl of 1 to 10 carbon atoms, alkenyl or alkynyl of 3 to 10 carbon atoms in which the double or triple bond respectively is separated from the nitrogen atom to which the radical is attached by at least one carbon atom, cycloalkyl of 3 to 8 carbon atoms, (primary hydroxy)alkyl of 2 to 6 carbon atoms, alkoxyalkyl of 3 to 10 carbon atoms in which the oxygen atom is separated from the nitrogen atom to which the radical is attached by at least two carbon atoms, or alkylamino or dialkylamino of 3 to 10 and 4 to 10 carbon atoms respectively in which the nitrogen atom is separated from the nitrogen atom to which the radical is attached by at least two carbon atoms, and G is alkylene of 2 to 12 carbon atoms, alkenylene or alkynylene of 4 to 12 carbon atoms in which the double and triple bonds respectively are separated from E.sup.1 and E.sup.2 by at least one carbon atom, or hydroxyalkylene of 3 to 12 carbon atoms in which the hydroxy substituent is carried on a carbon atom which is separated from E.sup.1 and E.sup.2 by at least one carbon atom; PA1 Het.sup.1 is an oxazol-4-yl, thiazol-4-yl or imidazol-4-yl radical substituted in the 2-position by a radical of the formula: ##STR11## or Het.sup.1 is a 1,2,4-thiadiazol-3-yl or 1,2,4-oxadiazol-3-yl radical substituted in the 5-position by a radical of the formula III, in which R.sup.5 is hydrogen, alkyl of 1 to 10 carbon atoms, alkanoyl of 1 to 6 carbon atoms or aroyl of 7 to 11 carbon atoms; PA1 Het.sup.2 is one of the values given above for Het.sup.1 or is an unfused nitrogen-containing 5- or 6-membered monocyclic heterocyclic ring which is optionally substituted by alkyl or alkoxy of 1 to 6 carbon atoms, hydroxy, trifluoromethyl, hydroxymethyl, amino or halogen, or Het.sup.2 is a radical of the formula: ##STR12## in which B is straight- or branched-chain alkylene of 1 to 6 carbon atoms and R.sup.6 and R.sup.7, which may be the same or different, are hydrogen, alkyl of 1 to 8 carbon atoms, alkenyl or cycloalkyl of 3 to 8 carbon atoms, alkoxyalkyl, alkylaminoalkyl or dialkylaminoalkyl of 3 to 10 carbon atoms in which the oxygen and nitrogen atoms respectively are separated from the nitrogen atom of NR.sup.6 R.sup.7 by at least two carbon atoms, or phenylalkyl of 7 to 12 carbon atoms optionally substituted on the phenyl ring by alkyl or alkoxy of 1 to 6 carbon atoms or by halogen, or R.sup.6 and R.sup.7 may be joined together to form a 5- or 6-membered saturated ring which may optionally contain an oxygen or additional nitrogen atom, the additional nitrogen atom being substituted by a hydrogen atom or an alkyl radical of 1 to 6 carbon atoms; PA1 provided that when R.sup.1 and R.sup.2 are both hydrogen and A is C.dbd.NH, Y.sup.1 and/or Y.sup.2 is a sulphur atom, and then when R.sup.1 and R.sup.2 are both hydrogen, A is C.dbd.NH and Het.sup.2 is imidazole, the number of atoms in the chain represented by: EQU (CH.sub.2).sub.q --Y.sup.2 --(CH.sub.2).sub.p PA1 is at least four; PA1 X is methylene, oxygen, sulfur or &gt;N--R.sup.6 in which R.sup.6 is hydrogen or methyl; n is 0, 1 or 2; m is 2, 3 or 4; R.sub.3 is hydrogen, alkyl, alkenyl, aralkyl, hydroxyalkyl having at least two carbon atoms, alkoxyalkyl or aryl; and R.sub.4 and R.sup.5 are independently hydrogen, alkyl, alkyl substituted by hydroxy or C.sub.1-3 alkoxy, alkenyl, aralkyl or heteroaralkyl, or R.sub.4 and R.sub.5 taken together with the nitrogen to which they are attached, may be a 5- to 7-membered saturated heterocyclic ring which may contain another heteroatom or the group &gt;NR.sup.6, or R.sub.4 and R.sub.5 taken together may be the group &gt;CR.sub.8 R.sub.9 wherein R.sub.8 is aryl or heteroaryl and R.sub.9 is hydrogen or alkyl; and physiologically acceptable salts and hydrates thereof. PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; and PA1 A is ##STR16## in which R.sup.6 is hydrogen, (lower)alkyl, (lower)alkoxy or halogen, and R.sup.7 is hydrogen or ##STR17## in which r is an integer of from 0 to 4 inclusive, and R.sup.8 and R.sup.9 each are independently hydrogen, (lower)alkyl, allyl, propargyl, (lower)alkoxy(lower)alkyl in which the (lower)alkoxy moiety is at least two carbon atoms removed from the nitrogen atom, cyclo(lower)alkyl, or phenyl(lower)alkyl, provided that R.sup.8 and R.sup.9 may not both be cyclo(lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, dimethylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, dimethylpiperidino, hydroxypiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino; and PA1 R.sup.10 is the same as R.sup.7 or is ##STR18## in which R.sup.11 is hydrogen or (lower)alkyl; PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; and PA1 A is ##STR24## in which R.sup.6 is hydrogen, (lower)alkyl or (lower)alkoxy, and R.sup.7 is hydrogen or ##STR25## in which r is an integer of from 0 to 4 inclusive, and R.sup.8 and R.sup.9 each are independently hydrogen or (lower)alkyl; or, R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino; and PA1 R.sup.10 is the same as R.sup.7 or is ##STR26## in which R.sup.11 is hydrogen or (lower)alkyl; PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; PA1 R.sup.6 is hydrogen or (lower)alkyl; and PA1 R.sup.7 is hydrogen or ##STR28## in which r is an integer of from 0 to 4 inclusive, and R.sup.8 and R.sup.9 each are independently hydrogen or (lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino; PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; PA1 R.sup.6 is hydrogen or (lower)alkyl; and PA1 R.sup.7 is hydrogen or ##STR30## in which r is an integer of from 0 to 4 inclusive, and R.sup.8 and R.sup.9 each are independently hydrogen or (lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino; PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; PA1 R.sup.6 is hydrogen or (lower)alkyl; and PA1 R.sup.10 is hydrogen, ##STR32## in which R.sup.11 is hydrogen or (lower)alkyl, R.sup.8 and R.sup.9 each are independently hydrogen or (lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino; PA1 (a) 1-amino-2-[3-(3-piperidinomethylphenoxy)propylamino]-cyclobutene-3,4-dione , or a nontoxic pharmaceutically acceptable salt, hydrate, solvate or N-oxide thereof (and particularly the hydrochloride thereof), PA1 (b) 1-amino-2-{2-[(5-dimethylaminomethyl-2-furyl)-methylthio]ethylamino}cyclob utene-3,4-dione, or a nontoxic pharmaceutically acceptable salt, hydrate, solvate or N-oxide thereof, and PA1 (c) 1-amino-2-{2-[(5-dimethylaminomethyl-2-thienyl)-methylthio]ethylamino}cycl obutene-3,4-dione, or a nontoxic pharmaceutically acceptable salt, hydrate, solvate or N-oxide thereof. PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; and PA1 A is ##STR34## in which R.sup.6 is hydrogen, (lower)alkyl, (lower)alkoxy or halogen, and R.sup.7 is hydrogen or ##STR35## in which r is an integer of from 0 to 4 inclusive, and R.sup.8 and R.sup.9 each are independently hydrogen, (lower)alkyl, allyl, propargyl, (lower)alkoxy(lower)alkyl in which the (lower)alkoxy moiety is at least two carbon atoms removed from the nitrogen atom, cyclo(lower)alkyl, or phenyl(lower)alkyl, provided that R.sup.8 and R.sup.9 may not both be cyclo(lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, dimethylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, dimethylpiperidino, hydroxypiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino; and PA1 R.sup.10 is the same as R.sup.7 or is ##STR36## in which R.sup.11 is hydrogen or (lower)alkyl. PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; PA1 R.sup.6 is hydrogen or (lower)alkyl; and PA1 R.sup.7 is hydrogen or ##STR38## in which r is an integer of from 0 to 4 inclusive, and R.sup.8 and R.sup.9 each are independently hydrogen or (lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino. PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; PA1 R.sup.6 is hydrogen or (lower)alkyl; and PA1 R.sup.7 is hydrogen or ##STR40## in which r is an integer of from 0 to 4 inclusive, and R.sup.8 and R.sup.9 each are independently hydrogen or (lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethyleneimino. PA1 m is an integer of from 0 to 2 inclusive; PA1 n is an integer of from 2 to 4 inclusive; PA1 Z is sulfur, oxygen or methylene; PA1 R.sup.6 is hydrogen or (lower)alkyl; and PA1 R.sup.10 is hydrogen, ##STR42## in which R.sup.11 is hydrogen or (lower)alkyl, R.sup.8 and R.sup.9 each are independently hydrogen or (lower)alkyl; or R.sup.8 and R.sup.9, taken together with the nitrogen atom to which they are attached, may be pyrrolidino, methylpyrrolidino, morpholino, thiomorpholino, piperidino, methylpiperidino, N-methylpiperazino, homopiperidino, heptamethyleneimino or octamethylleneimino. PA1 (a) 1-methoxy-2-[3-(3-piperidinomethylphenoxy)propylamino]-cyclobutene-3,4-dio ne, PA1 (b) 1-methoxy-2-{2-[(5-dimethylaminomethyl-2-furyl)-methylthio]ethylamino}cycl obutene-3,4-dione, and PA1 (c) 1-methoxy-2-{2-[(5-dimethylaminomethyl-2-thienyl)-methylthio]ethylamino}cy clobutene-3,4-dione.
Published European Patent Application 6,679 has a disclosure which is substantially the same as U.S. Pat. No. 4,242,350.
(C) U.K. Published Patent Application 2,001,624 discloses histamine H.sub.2 -antagonists of the formula ##STR5## in which X is sulphur or NH; Y is oxygen, sulphur, a direct bond, a methylene or sulphinyl radical or a cis or trans-vinylene radical;
U.S. Pat. Nos. 4,165,377 and 4,234,735 have disclosures which are substantially the same as U.K. Pat. No. 2,001,624, except that Y may not be oxygen, sulfur or a sulfinyl radical.
U.S. Pat. No. 4,165,378 has a disclosure which is substantially the same as U.K. Pat. No. 2,001,624, except that Y may not be a direct bond, a methylene radical or a vinylene radical.
(D) U.S. Pat. No. 4,242,351 discloses histamine H.sub.2 -antagonists of the formula ##STR6## in which Y is an oxygen or sulphur atom, a direct bond or a methylene radical; m is 0 to 4 and n is 1 to 4, provided that when Y is a sulphur or oxygen atom m is 1 to 4, and when Y is an oxygen atom n is 2 to 4;
Published European Patent Application 6,286 has a disclosure which is substantially the same as U.S. Pat. No. 4,242,351.
(E) Published European Patent Application 14,057 discloses histamine H.sub.2 -antagonists of the formula ##STR7## in which X is oxygen or sulphur;
(F) Published European Patent Application 3,640 discloses histamine H.sub.2 -antagonists of the formula ##STR10## in which X is oxygen or sulphur;
and the pharmaceutically-acceptable acid-addition salts thereof.
(G) Published European Patent Application 10,418 discloses histamine H.sub.2 -antagonists of the formula EQU Het.sup.1 -(CH.sub.2).sub.m --Y.sup.1 --(CH.sub.2).sub.n --NR.sup.1 --A--NR.sup.2 --(CH.sub.2).sub.1 --Y.sup.2 --(CH.sub.2).sub.p --Het.sup.2
in which
and the pharmaceutically-acceptable acid addition salts thereof.
(H) U.K. Published Patent Application 2,023,133 discloses histamine H.sub.2 -antagonists of the formula ##STR13## wherein R.sub.1 and R.sub.2 are independently hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aralkyl, trifluoroalkyl or alkyl substituted by hydroxy, alkoxy, amino, alkylamino, dialkylamino or cycloalkyl, or R.sub.1 and R.sup.2, taken together with the nitrogen to which they are attached, may be a 5- to 10-membered alicyclic heterocyclic ring which may be saturated or may contain at least one double bond, which may be substituted by one or more alkyl groups or a hydroxy group and/or which may contain another heteroatom; Alk is a straight or branched alkylene chain of 1-6 carbon atoms; Q is a furan or thiophene ring incorporated into the molecule via the 2- and 5-positions, the furan ring optionally bearing a further substituent R.sub.7 adjacent the R.sub.1 R.sub.2 N-Alk- group, or Q is a benzene ring incorporated into the molecule via its 1- and 3- or 1- and 4-positions; R.sub.7 is halogen, alkyl (which may be substituted by hydroxy or alkoxy);